Abstract

Background

Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between
the obesity-risk alleles with type 2 diabetes is still controversial. In some recent
meta-analyses in which significant results have been reported, the associations disappeared
after adjustment for body mass index (BMI). However gene-diet interactions with dietary
patterns have not been investigated. Our main aim was to analyze whether these associations
are modulated by the level of adherence to the Mediterranean Diet (MedDiet).

Results

Neither of the polymorphisms was associated with type 2 diabetes in the whole population.
However, we found consistent gene-diet interactions with adherence to the MedDiet
both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006).
When adherence to the MedDiet was low, carriers of the variant alleles had higher
type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high,
these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment
for BMI. As MedDiet is rich in folate, we also specifically examined folate intake
and detected statistically significant interaction effects on fasting plasma glucose
concentrations in non-diabetic subjects. However these findings should be interpreted
with caution because folate intake may simply reflect a healthy dietary pattern.

Conclusions

These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence
to the MedDiet counteracts the genetic predisposition.